Search

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial (MT) Chromosomes. We genotyped the Y and MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. We identified 8 distinct Y and 4 distinct MT Chromosomes among the 8 founders. However, only 2 types of each nonrecombinant chromosome were observed in our modern HS rat population (generations 81-97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and MT Chromosomes were strongly associated with the expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern HS rats there are no Y and MT Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and MT Chromosomes that do not appear in modern HS rats, nor do they address effects that may exist in other rat populations, or in other species.

The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome complement). FCG mice have illuminated distinct effects of gonadal and chromosomal sex on traits ranging from brain structure and behavior to vulnerability to obesity, atherosclerosis, multiple sclerosis, Alzheimers and other diseases. A recent study determined that the YSry- chromosome used in a specific line of C57BL/6J FCG mice harbors nine genes that have been duplicated from the X chromosome. This report raised concern that scores of publications that previously used the FCG model may therefore be flawed, but did not provide details regarding how studies can be evaluated for potential impact (or lack of impact) of the translocation. Here we (1) provide a practical description of the genetic translocation for researchers using the FCG model, (2) document that a majority of the studies cited in the recent report are unlikely to be affected by the translocation, (3) provide a scheme for interpreting data from studies with FCG mice harboring the YSry- translocation, and (4) delineate expression levels of the nine translocated genes across tissue/cell types as a filter for evaluating their potential involvement in specific phenotypes.

ABSTRACT Alternative reproductive tactics are discrete, intrasexual differences in reproductive behaviour within a population. In some cases, these complex phenotypes are determined by autosomal supergenes or sex chromosomes—both of which exhibit reduced recombination and thus enable the linked inheritance of co‐adapted alleles from multiple loci. Most alternative reproductive tactics in amphibians are plastic (and reversible), environmentally determined and lacking morphological differentiation, but a striking exception is found in the two‐lined salamander (Eurycea bislineata) species complex. In some populations, two distinct male phenotypes coexist: ‘searching’ males have mental glands, protruding premaxillary teeth and elongate cirri used in terrestrial courtship, while ‘guarding’ males lack these traits and instead have hypertrophied jaw musculature used in mate guarding at aquatic nesting sites. These tactics differ in many morphological and behavioural phenotypes, but their proximate cause has not yet been described. Here, we generated genome‐wide SNP data from > 130 Eurycea cf. wilderae collected from Highlands Biological Station. We provide evidence for an XY sex determination and for a Y‐linked polymorphism underlying alternative reproductive tactics in this population. We then develop and validate a PCR‐based genotyping assay and apply it to characterise the sex ratio and relative frequency of male tactics from a sample of larvae. Our results add to the growing body of literature exploring the importance of supergenes and sex chromosomes in complex intraspecific polymorphisms, and we highlight opportunities for future work to continue exploring the genomic architecture of these traits. [ABSTRACT FROM AUTHOR]

The early evolution of sex chromosomes has remained obscure for more than a century. The Vandiemenella viatica species group of morabine grasshoppers is highly suited for studying the early stages of sex chromosome divergence and degeneration of the Y chromosome. This stems from the fact that neo‐XY sex chromosomes have independently evolved multiple times by X‐autosome fusions with different autosomes. Here, we generated new chromosome‐level assemblies for two chromosomal races representing karyotypes with and without neo‐sex chromosomes (P24XY and P24X0), and sequence data of a third chromosomal race with a different neo‐XY chromosome system (P25XY). Interestingly, these two neo‐XY chromosomal races are formed by different X‐autosome fusions (involving chr1 and chrB, respectively), and we found that both neo‐Y chromosomes have partly ceased to recombine with their neo‐X counterpart. We show that the neo‐XY chromosomes have diverged through accumulation of SNPs and structural mutations, and that many neo‐Y‐linked genes have degenerated since recombination ceased. However, the non‐recombining regions of neo‐Y chromosomes host non‐degenerated genes crucial for sex determination, such as sex‐lethal and transformer, alongside genes associated with spermatogenesis, fertility, and reproduction, illustrating their integrative role as a masculinizing supergene. Contrary to expectations, the neo‐Y chromosomes showed (slightly) lower density of transposable elements (TEs) compared to other genomic regions. The study reveals the unique dynamics of young sex chromosomes, with evolution of recombination suppression and pronounced decay of (some) neo‐sex chromosome genes, and provides a compelling case illustrating how chromosomal fusions and post‐fusion mutational processes contribute to the evolution of supergenes. [ABSTRACT FROM AUTHOR]

Sex-ratio meiotic drivers are selfish genes or gene complexes that bias the transmission of sex chromosomes resulting in skewed sex ratios. Existing theoretical models have suggested the maintenance of a four-chromosome equilibrium (with driving and standard X and suppressing and susceptible Y) in a cyclic dynamic, but studies of natural populations have failed to capture this pattern. Although there are several plausible explanations for this lack of cycling, interference from autosomal suppressors has not been studied using a theoretical population genetic framework even though autosomal suppressors and Y-linked suppressors coexist in natural populations of some species. In this study, we use a simulation-based approach to investigate the influence of autosomal suppressors on the cycling of sex chromosomes. Our findings demonstrate that the presence of an autosomal suppressor can hinder the invasion of a Y-linked suppressor under some parameter space, thereby impeding the cyclic dynamics, or even the invasion of Y-linked suppression. Even when a Y-linked suppressor invades, the presence of an autosomal suppressor can prevent cycling. Our study demonstrates the potential role of autosomal suppressors in preventing sex chromosome cycling and provides insights into the conditions and consequences of maintaining both Y-linked and autosomal suppressors. [ABSTRACT FROM AUTHOR]

The XX/XY sex chromosome system is deeply conserved in therian mammals, as is the role of Sry in testis determination, giving the impression of stasis relative to other taxa. However, the long tradition of cytogenetic studies in mammals documents sex chromosome karyotypes that break this norm in myriad ways, ranging from fusions between sex chromosomes and autosomes to Y chromosome loss. Evolutionary conflict, in the form of sexual antagonism or meiotic drive, is the primary predicted driver of sex chromosome transformation and turnover. Yet conflict-based hypotheses are less considered in mammals, perhaps because of the perceived stability of the sex chromosome system. To address this gap, we catalog and characterize all described sex chromosome variants in mammals, test for family-specific rates of accumulation, and consider the role of conflict between the sexes or within the genome in the evolution of these systems. We identify 152 species with sex chromosomes that differ from the ancestral state and find evidence for different rates of ancestral to derived transitions among families. Sex chromosome-autosome fusions account for 79% of all variants whereas documented sex chromosome fissions are limited to three species. We propose that meiotic drive and drive suppression provide viable explanations for the evolution of many of these variant systems, particularly those involving autosomal fusions. We highlight taxa particularly worthy of further study and provide experimental predictions for testing the role of conflict and its alternatives in generating observed sex chromosome diversity. [ABSTRACT FROM AUTHOR]

We present evidence implicating the BAF (BRG1/BRM Associated Factor) chromatin remodeler in meiotic sex chromosome inactivation (MSCI). By immunofluorescence (IF), the putative BAF DNA binding subunit, ARID1A (AT-rich Interaction Domain 1 a), appeared enriched on the male sex chromosomes during diplonema of meiosis I. Germ cells showing a Cre-induced loss of ARID1A arrested in pachynema and failed to repress sex-linked genes, indicating a defective MSCI. Mutant sex chromosomes displayed an abnormal presence of elongating RNA polymerase II coupled with an overall increase in chromatin accessibility detectable by ATAC-seq. We identified a role for ARID1A in promoting the preferential enrichment of the histone variant, H3.3, on the sex chromosomes, a known hallmark of MSCI. Without ARID1A, the sex chromosomes appeared depleted of H3.3 at levels resembling autosomes. Higher resolution analyses by CUT & RUN revealed shifts in sex-linked H3.3 associations from discrete intergenic sites and broader gene-body domains to promoters in response to the loss of ARID1A. Several sex-linked sites displayed ectopic H3.3 occupancy that did not co-localize with DMC1 (DNA meiotic recombinase 1). This observation suggests a requirement for ARID1A in DMC1 localization to the asynapsed sex chromatids. We conclude that ARID1A-directed H3.3 localization influences meiotic sex chromosome gene regulation and DNA repair. [ABSTRACT FROM AUTHOR]

Beetles are the most species-rich group of animals and harbor diverse karyotypes. Most species have XY sex chromosomes, but X0 sex determination mechanisms are also common in some groups. We generated a whole-chromosome assembly of Tribolium confusum, which has a neo-sex chromosome, and utilize eleven additional beetle genomes to reconstruct karyotype evolution across Coleoptera. We identify ancestral linkage groups, termed Stevens elements, that share a conserved set of genes across beetles. While the ancestral X chromosome is maintained across beetles, we find independent additions of autosomes to the ancestral sex chromosomes. These neo-sex chromosomes evolve the stereotypical properties of sex chromosomes, including the evolution of dosage compensation and a non-random distribution of genes with sex-biased expression. Beetles thus provide a novel model to gain a better understanding of the diverse forces driving sex chromosome evolution. Author summary: The evolution of differentiated sex chromosomes (e.g., X and Y chromosomes in male heterogametic species) from ordinary autosomes has occurred many times in animals and plants. Investigation of sex chromosomes in key model species (such as mammals, birds, flies and worms) has revealed that sex chromosome evolution is driven by both general and lineage-specific forces, but a detailed investigation and understanding of sex chromosomes from many clades is lacking. Importantly, cytogenetic studies in beetles–the most species-rich group of animals—have shown that chromosomal sex determination is conserved across Coleoptera. However, the identity and conservation of sex chromosomes in beetles at the molecular level and the evolutionary processes shaping them have not been studied in a systematic way. We use genomic approaches to understand karyotype and sex chromosome evolution across Coleoptera to establish general principles underlying the evolution of sex chromosomes in the most speciose group of animals on earth. [ABSTRACT FROM AUTHOR]

Nomascus leucogenys is a critically endangered species of small apes. Here, we sequenced and assembled the male genome of N. leucogenys, using PacBio and Hi-C datasets, with a particular focus on its Y-chromosome. The resulting high-quality haplotype-phased assemblies are at chromosome-scale, with scaffold/contig N50 values of 124.2/102.2 Mb for Haplotype 1 and 121.2/85.67 Mb for Haplotype 2. The assembled Y-chromosome spans 16.06 Mb. BUSCO assessment indicated completeness scores exceeding 95%. We predicted 18,925 protein-coding genes (23,783 mRNAs), including 58 genes on the Y-chromosome. Approximately 50% of the genome comprises repetitive elements. These comprehensive genome datasets will serve as a valuable resource for future studies on the genetics and protection of gibbons and improve our understanding on the evolution of Y-chromosome-related genes in primates. [ABSTRACT FROM AUTHOR]

Centromeres reside in rapidly evolving, repeat-rich genomic regions, despite their essential function in chromosome segregation. Across organisms, centromeres are rich in selfish genetic elements such as transposable elements and satellite DNAs that can bias their transmission through meiosis. However, these elements still need to cooperate at some level and contribute to, or avoid interfering with, centromere function. To gain insight into the balance between conflict and cooperation at centromeric DNA, we take advantage of the close evolutionary relationships within the Drosophila simulans clade—D. simulans, D. sechellia, and D. mauritiana—and their relative, D. melanogaster. Using chromatin profiling combined with high-resolution fluorescence in situ hybridization on stretched chromatin fibers, we characterize all centromeres across these species. We discovered dramatic centromere reorganization involving recurrent shifts between retroelements and satellite DNAs over short evolutionary timescales. We also reveal the recent origin (<240 Kya) of telocentric chromosomes in D. sechellia, where the X and fourth centromeres now sit on telomere-specific retroelements. Finally, the Y chromosome centromeres, which are the only chromosomes that do not experience female meiosis, do not show dynamic cycling between satDNA and TEs. The patterns of rapid centromere turnover in these species are consistent with genetic conflicts in the female germline and have implications for centromeric DNA function and karyotype evolution. Regardless of the evolutionary forces driving this turnover, the rapid reorganization of centromeric sequences over short evolutionary timescales highlights their potential as hotspots for evolutionary innovation. Centromeres reside in rapidly evolving, repeat-rich genomic regions, despite their essential function in chromosome segregation. This study of centromere evolution over short evolutionary timescales in Drosophila reveals dramatic centromere reorganization involving recurrent shifts between retroelements and satellite DNAs. [ABSTRACT FROM AUTHOR]

Pigs play a central role in human livelihoods in China, but a lack of systematic large-scale whole-genome sequencing of Chinese domestic pigs has hindered genetic studies. Here, we present the 1000 Chinese Indigenous Pig Genomes Project sequencing dataset, comprising 1011 indigenous individuals from 50 pig populations covering approximately two-thirds of China's administrative divisions. Based on the deep sequencing (~25.95×) of these pigs, we identify 63.62 million genomic variants, and provide a population-specific reference panel to improve the imputation performance of Chinese domestic pig populations. Using a combination of methods, we detect an ancient admixture event related to a human immigration climax in the 13th century, which may have contributed to the formation of southeast-central Chinese pig populations. Analyzing the haplotypes of the Y chromosome shows that the indigenous populations residing around the Taihu Lake Basin exhibit a unique haplotype. Furthermore, we find a 13 kb region in the THSD7A gene that may relate to high-altitude adaptation, and a 0.47 Mb region on chromosome 7 that is significantly associated with body size traits. These results highlight the value of our genomic resource in facilitating genomic architecture and complex traits studies in pigs. Here the authors describe a genomic dataset, the1000 Chinese Indigenous Pig Genomes Project (1KCIGP), based on the whole-genome sequencing of 1,011 Chinese domestic pigs from 50 distinct populations, which provides insights into the genomic architecture of domestic pigs. [ABSTRACT FROM AUTHOR]

We have used multiple sequencing approaches to sequence the genome of a volunteer from Saudi Arabia. We use the resulting data to generate a de novo assembly of the genome, and use different computational approaches to refine the assembly. As a consequence, we provide a contiguous assembly of the complete genome of an individual from Saudi Arabia for all chromosomes except chromosome Y, and label this assembly KSA001. We transferred genome annotations from reference genomes to fully annotate KSA001, and we make all primary sequencing data, the assembly, and the genome annotations freely available in public databases using the FAIR data principles. KSA001 is the first telomere-to-telomere-assembled genome from a Saudi individual that is freely available for any purpose. [ABSTRACT FROM AUTHOR]

A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP). Species genomes are important for analyses of genetic variation. Wu et al. assembled a T2T genome of a male cashmere goat, including 288.5 Mb of previously unresolved regions, and identified selective variants and genes associated with domestication and cashmere traits. [ABSTRACT FROM AUTHOR]

The Y chromosomal haplotype is expected to be identical (or close to, depending on the mutation rate) among a male and many of his paternal relatives. This means that often the same evidential value for the DNA evidence is obtained, whether the true donor or one of his close paternal relatives is compared to a crime sample. Commentators (see for example the UK Forensic Science Regulator or Amorim) have suggested to change the proposition pair to compare the probability of the evidence if the Person of Interest (POI) or one of his close paternal relatives left the DNA to the probability of the evidence if an unrelated male from the population left the DNA. We argue that this is problematic because there is no clear definition of close paternal relatives and truly unrelated males do not exist. Instead, we take a starting point in the traditional proposition pair “The source of the male DNA is the POI” versus “The source of the male DNA is not the POI” and make the latter one operational by suggesting that it is formulated as “The source of the male DNA is a random man from the population”. The issue of matching males in the POI's lineage is then addressed either in a comment in the statement or directly through a probability model. [ABSTRACT FROM AUTHOR]

Simple Summary: This research examines how the loss of the Y chromosome (LoY) in men may contribute to the development and progression of certain cancers, particularly in the urinary system. Traditionally, the Y chromosome was primarily associated with male sex determination and sperm production, but recent studies suggest it plays a wider role in health and disease. LoY appears to disrupt immune function and increase genetic instability, factors that may heighten cancer risk and impact treatment outcomes. Our review highlights that LoY could serve as an early indicator of certain cancers and might help predict cancer behavior. Understanding LoY's role could lead to new diagnostic tools and treatments, especially for cancers where Y chromosome alterations are linked to poorer outcomes. Background: The Y chromosome (ChrY) is essential for male sex determination and spermatogenesis. However, recent studies have revealed its broader role in various physiological processes and disease susceptibility, including cancer. Methods: A comprehensive literature review was conducted using databases like MEDLINE, Scopus, Web of Science, and Google Scholar. The review included clinical and preclinical studies in animals and humans focusing on the role of LoY in urological tumors. Data on the frequency of LoY, its clinical implications, and underlying mechanisms were extracted and analyzed. Results: The evidence suggests that LoY is associated with an increased risk of urologic neoplasms, potentially serving as an early marker of genomic instability. Studies reveal that LoY in urologic cancers correlates with worse survival outcomes and may contribute to tumor progression. LoY may interfere with chromatin structure and epigenetic regulation, suggesting its role as a contributor to early tumorigenesis. Conclusions: LoY appears to be a structural aberration with unique biological and clinical relevance in urologic cancers, possibly serving as a biomarker for genomic instability. Further research is necessary to identify specific Y-linked genes affected by LoY, potentially informing targeted therapies and early diagnostic strategies for these cancers. [ABSTRACT FROM AUTHOR]

Background: Interphase fluorescence in situ hybridization (FISH) is commonly used for rapid aneuploidy detection in clinical settings. While FISH-based aneuploidy detection provides rapid results desirable for patient management, it usually only utilizes one probe per chromosome, which may lead to rare false-positive findings. Case presentation: Here we report two interphase FISH results, which were false-positive for XXY in cytogenetically normal XX individuals. Both false-positive cases were due to hybridization of the Y chromosome centromeric probe DYZ3 to the pericentromeric region of chromosome 15. In both cases, chromosomal microarray revealed no detectable Y chromosome material, suggesting the hybridizations of the DYZ3 probe to chromosome 15 likely represent benign heterochromatic variants of no clinical significance. In one case, the DYZ3 hybridization was also identified in the phenotypically unaffected mother, further suggesting this is likely a rare variant of no clinical significance. Conclusions: This report marks the first documentation of hybridization of the DYZ3 probe to another chromosome in cytogenetically normal individuals. Our report has important clinical implications, because DYZ3 is widely used by clinical laboratories for Y chromosome detection. Our findings underscore the necessity of confirming abnormal aneuploidy detection FISH results with additional laboratory methods such as chromosomal microarray analysis. [ABSTRACT FROM AUTHOR]

A recent publication describing the assembly of the Y chromosomes of 43 males was remarkable not only for its ambitious technical scope but also for the startling suggestion that the boundary of the pseudoautosomal region 1 (PAR1), where the human X and Y chromosomes engage in crossing-over during male meiosis, lies 500 kb distal to its previously reported location. Where is the boundary of the human PAR1? We first review the evidence that mapped the PAR boundary, or PAB, before the human genome draft sequence was produced, then examine post-genomic datasets for evidence of crossing-over between the X and Y, and lastly re-examine contiguous sequence assemblies of the PAR-NPY boundary to see whether they support a more distal PAB. We find ample evidence of X-Y crossovers throughout the 500 kb in question, some as close as 246 bp to the previously reported PAB. Our new analyses, combined with previous studies over the past 40 years, provide overwhelming evidence to support the original position and narrow the probable location of the PAB to a 201-bp window. [Display omitted] Controversy has arisen regarding a landmark on the human sex chromosomes—the pseudoautosomal boundary—with recent analyses suggesting a location 500 kb distal to that reported in 1989. Our multifaceted analyses of the available data consistently validate the original position, narrowing the location of the boundary to a 201-bp window. [ABSTRACT FROM AUTHOR]

Phylogenomics has the power to uncover complex phylogenetic scenarios across the genome. In most cases, no single topology is reflected across the entire genome as the phylogenetic signal differs among genomic regions due to processes, such as introgression and incomplete lineage sorting. Baleen whales are among the largest vertebrates on Earth with a high dispersal potential in a relatively unrestricted habitat, the oceans. The fin whale (Balaenoptera physalus) is one of the most enigmatic baleen whale species, currently divided into four subspecies. It has been a matter of debate whether phylogeographic patterns explain taxonomic variation in fin whales. Here we present a chromosome-level whole genome analysis of the phylogenetic relationships among fin whales from multiple ocean basins. First, we estimated concatenated and consensus phylogenies for both the mitochondrial and nuclear genomes. The consensus phylogenies based upon the autosomal genome uncovered monophyletic clades associated with each ocean basin, aligning with the current understanding of subspecies division. Nevertheless, discordances were detected in the phylogenies based on the Y chromosome, mitochondrial genome, autosomal genome and X chromosome. Furthermore, we detected signs of introgression and pervasive phylogenetic discordance across the autosomal genome. This complex phylogenetic scenario could be explained by a puzzle of introgressive events, not yet documented in fin whales. Similarly, incomplete lineage sorting and low phylogenetic signal could lead to such phylogenetic discordances. Our study reinforces the pitfalls of relying on concatenated or single locus phylogenies to determine taxonomic relationships below the species level by illustrating the underlying nuances that some phylogenetic approaches may fail to capture. We emphasize the significance of accurate taxonomic delineation in fin whales by exploring crucial information revealed through genome-wide assessments. [ABSTRACT FROM AUTHOR]

In mammals, sex determination is governed by the SRY gene on the Y chromosome, redirecting gonadal development from forming ovaries to testes. Mutations or alterations in the SRY gene can significantly affect phenotypic changes and lineage‐specific markers. This study aims to elucidate the role of the SRY gene in buffalo embryos using CRISPR‐Cas9 technology. We designed a crRNA targeting the HMG domain of the SRY gene using the CRISPOR algorithm. Nucleofection of sgRNA‐Cas9 RNPs into buffalo fibroblasts confirmed efficient cleavage at the targeted site. Using this validated guide, we investigated the role of the SRY gene in sexual determination by electroporating CRISPR‐Cas9‐RNPs into single‐stage zygotes of buffalo. Genetic changes in the SRY gene were confirmed through sequencing, revealing mosaic blastocysts with multiple alleles and non‐mosaic mutants. Mutations in SRY gene increased the expression of female lineage‐specific gene Wnt4 whereas decreased the expression of male specific gene SOX9 in blastocysts, suggesting reprogramming towards female sex determination pathways. Our findings provide insights into buffalo sex differentiation mechanisms and potential applications in reproductive strategies for breeding programmes. [ABSTRACT FROM AUTHOR]

Background: When the SRY gene is present in a 46,XX fetus, some degree of testicular development is expected. Our laboratory performed prenatal genetic testing for a fetus that had screened positive for Y chromosome material by noninvasive prenatal screening (NIPS) but that had apparently typical female development by ultrasound imaging. The aim of this study was to determine the clinical relevance of the NIPS results. Methods: We analyzed fetal material obtained via amniocentesis procedure by G‐banding, microarray, and fluorescence in situ hybridization (FISH). Optical genome mapping (OGM) was also performed. Results: G‐band analysis revealed a normal 46,XX karyotype. Microarray and FISH analyses together detected an SRY+ gain of 5.7 Mb from terminal Yp that was translocated to terminal Xq, with a loss of 1.6 Mb from terminal Xq. The final karyotype was 46,X,der(X)t(X;Y)(q28;p11.2). Prenatal ultrasound and postnatal physical examination revealed apparently typical female genitalia. The Xq deletion encompassed a gene, IKBKG, that is sensitive to loss of function, suggesting that preferential inactivation of the derivative X chromosome allowed for typical female development. OGM software did not directly identify this translocation. Conclusion: This case demonstrates how the SRY gene may be present in a 46,XX biological female without differences of sexual development. [ABSTRACT FROM AUTHOR]

Summary: Structural variations (SVs) are major genetic variants that can be involved in the origin, adaptation and domestication of species. However, the identification and characterization of SVs in Spinacia species are rare due to the lack of a pan‐genome. Here, we report eight chromosome‐scale assemblies of cultivated spinach and its two wild species. After integration with five existing assemblies, we constructed a comprehensive Spinacia pan‐genome and identified 193 661 pan‐SVs, which were genotyped in 452 Spinacia accessions. Our pan‐SVs enabled genome‐wide association study identified signals associated with sex and clarified the evolutionary direction of spinach. Most sex‐linked SVs (86%) were biased to occur on the Y chromosome during the evolution of the sex‐linked region, resulting in reduced Y‐linked gene expression. The frequency of pan‐SVs among Spinacia accessions further illustrated the contribution of these SVs to domestication, such as bolting time and seed dormancy. Furthermore, compared with SNPs, pan‐SVs act as efficient variants in genomic selection (GS) because of their ability to capture missing heritability information and higher prediction accuracy. Overall, this study provides a valuable resource for spinach genomics and highlights the potential utility of pan‐SV in crop improvement and breeding programmes. [ABSTRACT FROM AUTHOR]

The PowerPlex® 35GY System (Promega, USA) is an advanced eight-dye multiplex STR kit, incorporating twenty-three autosomal STR loci, eleven Y chromosome STR loci, one sex determining marker Amelogenin, and two quality indicators. This multiplex system includes 20 CODIS loci and up to 15 mini-STR loci with sizing values less than 250 bases. In this study, validation for PowerPlex® 35GY System was conducted following the guidelines of SWGDAM, encompassing sensitivity, precision, accuracy, concordance, species specificity, stutter, mixture, stability, and degraded DNA. The results from experiments demonstrated that the PowerPlex® 35GY System could effectively amplify DNA samples, with complete allele detection achieved at 125 pg. Moreover, over 90% of alleles from minor contributors were detected at a mixed ratio of 1:4. Additionally, the system was found to yield full profiles even in the presence of hematin, humic acid, and indigo. The PowerPlex® 35GY System demonstrated superior performance in the sensitivity and degraded DNA studies compared to a six-dye STR kit. Hence, it is evident that the PowerPlex® 35GY System is well-suited for forensic practice, whether in casework or for database samples. These findings provide strong support for the efficacy and reliability of the PowerPlex® 35GY System in forensic applications. [ABSTRACT FROM AUTHOR]

Aim: Whether widespread gene flow among primates is emblematic of their initial radiation or resulted from secondary contactremains a long‐standing question. We address this question on 'sinica' group macaques, highlighting the origin of the white‐cheeked macaque (Macaca leucogenys). Location: Eastern Himalayan highlands of Arunachal Pradesh, India. Taxon: Macaca leucogenys Li, Zhao, Fan, 2015b (Cercopithecidae). Methods: Mitochondrial genomes and Y‐chromosomal TSPY gene sequences of WCM were obtained from two distant populations through low‐depth genome sequencing. Phylogenetic analyses were conducted along with sequences of other available species within the genus Macaca. Results: We observed the presence of a single maternal lineage but two parental lineages. Interestingly, one paternal lineage of the white‐cheeked macaque clustered with a common lineage of M. assamensis and M. munzala. The other paternal lineage clustered with the sequences of the white‐cheeked macaque from the type locality in Southeastern Tibet. Main Conclusions: The result indicates a possible historic male‐mediated introgression in the white‐cheeked macaque, which is also present in the two other species belonging to the 'sinica' group. Therefore, extensive gene flow in 'sinica' group macaques possibly came from one or more introgression events in the past that also played a role in the origin and evolution of these macaque species. [ABSTRACT FROM AUTHOR]

The Y chromosome has long been considered to be a "genetic wasteland" harboring only few genes essentially involved in male sex development and spermatogenesis. However, the discovery of mosaic loss of the Y chromosome (mLOY) in older men has led to revisiting of the potential impact of the Y chromosome on health and the pathophysiological processes of multiple diseases such as cancer, Alzheimer's disease and cardiovascular disease. Hence, developing more sensitive techniques for the detection of mLOY has become an emergent concern. In this article, we present a comprehensive review of the literature regarding mLOY. Additionally, we discuss the emerging discoveries concerning mLOY as well as the underlying mechanisms promoting disease in men of advanced age. [ABSTRACT FROM AUTHOR]

Cytogenetic studies were carried out on 11 species of Indian Snakes collected from Jammu region using Air Drying Technique of Gorman et al 1979. Among all E. johni and E. conicus belonging to primitive family Boidae exhibits diploid number, 2n=34 with undifferentiated sex chromosomes in both male and female. In family Colubridae (an intermediate family) there exist huge variation as far as sex chromosomes are concerned i.e Ptyas mucosus has 2n=34, Oligodon arnensis has 2n=44 with undifferentiated sex chromosomes, Lycodon arnensis and Boiga trigonata both have 2n=36 with differentiated sex chromosomes(as per literature) while Natrix stolata has 2n=36 with distinct 'ZW' female. In Family Elapidae Naja naja naja has 2n=38 with undifferentiated sex chromosomes but Bungarus caerulus has 2n=44 with 'ZW' female having submetacentric 'Z' and largest telocentric 'W' but members of family Viperidae viz. Vipera russelli and Echinis carinatus both have 2n=36 with well differentiated 'ZW' where 'W' is smaller and 'Z' larger representing final step in the evolution of sex chromosome. [ABSTRACT FROM AUTHOR]

The male- limited inheritance of Y chromosomes favors alleles that increase male fitness, often at the expense of female fitness. Determining the mechanisms underlying these sexually antagonistic effects is challenging because it can require studying Y- linked alleles while they still segregate as polymorphisms. We used a Y chromosome polymorphism in the house fly, Musca domestica, to address this challenge. Two male determining Y chromosomes (YM and IIIM) segregate as stable polymorphisms in natural populations, and they differentially affect multiple traits, including male courtship performance. We identified differentially expressed genes encoding odorant binding proteins (in the Obp56h family) as candidate agents for the courtship differences. Through network analysis and allele- specific expression measurements, we identified multiple genes on the house fly IIIM chromosome that could serve as trans regulators of Obp56h gene expression. One of those genes is homologous to Drosophila melanogaster CG2120, which encodes a transcription factor that binds near Obp56h. Upregulation of CG2120 in D. melanogaster nervous tissues reduces copulation latency, consistent with this transcription factor acting as a negative regulator of Obp56h expression. The transcription factor gene, which we name speed date, demonstrates a molecular mechanism by which a Y- linked gene can evolve male- beneficial effects. [ABSTRACT FROM AUTHOR]

The human sex ratio (fraction of males) at birth is close to 0.5 at the population level, an observation commonly explained by Fisher's principle. However, past human studies yielded conflicting results regarding the existence of sex ratio-influencing mutations—a prerequisite to Fisher's principle, raising the question of whether the nearly even population sex ratio is instead dictated by the random X/Y chromosome segregation in male meiosis. Here we show that, because a person's offspring sex ratio (OSR) has an enormous measurement error, a gigantic sample is required to detect OSR-influencing genetic variants. Conducting a UK Biobank-based genome-wide association study that is more powerful than previous studies, we detect an OSR-associated genetic variant, which awaits verification in independent samples. Given the abysmal precision in measuring OSR, it is unsurprising that the estimated heritability of OSR is effectively zero. We further show that OSR's estimated heritability would remain virtually zero even if OSR is as genetically variable as the highly heritable human standing height. These analyses, along with simulations of human sex ratio evolution under selection, demonstrate the compatibility of the observed genetic architecture of human OSR with Fisher's principle and render it plausible that multiple OSR-influencing genetic variants segregate among humans. [ABSTRACT FROM AUTHOR]

The INO80 protein is the main catalytic subunit of the INO80-chromatin remodeling complex, which is critical for DNA repair and transcription regulation in murine spermatocytes. In this study, we explored the role of INO80 in silencing genes on meiotic sex chromosomes in male mice. INO80 immunolocalization at the XY body in pachytene spermatocytes suggested a role for INO80 in the meiotic sex body. Subsequent deletion of Ino80 resulted in high expression of sex-linked genes. Furthermore, the active form of RNA polymerase II at the sex chromosomes of Ino80-null pachytene spermatocytes indicates incomplete inactivation of sex-linked genes. A reduction in the recruitment of initiators of meiotic sex chromosome inhibition (MSCI) argues for INO80-facilitated recruitment of DNA repair factors required for silencing sex-linked genes. This role of INO80 is independent of a common INO80 target, H2A.Z. Instead, in the absence of INO80, a reduction in chromatin accessibility at DNA repair sites occurs on the sex chromosomes. These data suggest a role for INO80 in DNA repair factor localization, thereby facilitating the silencing of sex-linked genes during the onset of pachynema. Author summary: Chromatin accessibility is required for many DNA-protein interactions. Chromatin remodelers are the group of protein complexes that ensure the localized and timely unpacking of DNA to ensure access of a protein to its target DNA regions. The chromatin remodeler, INO80, has been implicated in many cellular processes, including transcription and DNA repair. We report that INO80 regulates the suppression of gene expression at the sex chromosomes in meiotic germ cells during mammalian spermatogenesis. INO80 localizes at the sex chromosomes during the pachynema stage, and its absence leads to a lack of suppression of gene expression at the sex chromosomes, which is known to be detrimental to meiotic progression. These genes were actively transcribed during pachynema in Ino80-mutant spermatocytes. DNA damage repair factors such as ATR and MDC1, which are instrumental in suppressing gene expression at the sex chromosomes during pachynema, were not localized properly in Ino80-mutant spermatocytes. Chromatin accessibility was also reduced at the DNA damage sites in sex chromosomes of the Ino80 mutants, which suggests a role for INO80 in the appropriate localization of DNA damage factors at accessible target sites to aid in the silencing of sex-linked genes during pachynema. [ABSTRACT FROM AUTHOR]

A female protective effect has long been postulated as the primary explanation for the four-fold increase of autism spectrum disorder (ASD) diagnoses in males versus females. However, genetic and epidemiological investigations of this hypothesis have so far failed to explain the large difference in ASD prevalence between the sexes. To address this knowledge gap, we examined sex chromosome aneuploidy in a large ASD case-control cohort to evaluate the relationship between X and Y chromosome dosage and ASD risk. From these data, we modeled three relationships between sex chromosome dosage and ASD risk: the extra Y effect, the extra X effect, and sex chromosome haploinsufficiency. We found that the extra Y effect increased ASD risk significantly more than the extra X effect. Among females, we observed a large association between 45, X and ASD, confirming sex chromosome haploinsufficiency as a strong ASD risk factor. These results provide a framework for understanding the relationship between X and Y chromosome dosage on ASD, which may inform future research investigating genomic contributors to the observed sex difference. Genetic and epidemiological investigations have yet to reveal what drives the large difference in ASD prevalence between the sexes. Here authors examine chromosome aneuploidy in a large ASD case-control cohort and report sex chromosome haploinsufficiency is a strong ASD risk factor, while the extra Y effect increases ASD risk significantly more than the extra X effect. [ABSTRACT FROM AUTHOR]

Stamens are vital reproductive organs in angiosperms, essential for plant growth, reproduction, and development. The genetic regulation and molecular mechanisms underlying stamen development are, however, complex and varied among different plant species. MSL-lncRNAs, a gene specific to the Y chromosome of Populus deltoides, is predominantly expressed in male flower buds. Heterologous expression of MSL-lncRNAs in Arabidopsis thaliana resulted in an increase in both stamen and anther count, without affecting pistil development or seed set. To reveal the molecular regulatory network influenced by MSL-lncRNAs on stamen development, we conducted transcriptome sequencing of flowers from both wild-type and MSL-lncRNAs-overexpressing Arabidopsis. A total of 678 differentially expressed genes were identified between wild-type and transgenic Arabidopsis. Among these, 20 were classified as transcription factors, suggesting a role for these regulatory proteins in stamen development. GO enrichment analysis revealed that the differentially expressed genes were significantly associated with processes such as pollen formation, polysaccharide catabolic processes, and secondary metabolism. KEGG pathway analysis indicated that MSL-lncRNAs might promote stamen development by upregulating genes involved in the phenylpropanoid biosynthesis pathway. The top three upregulated genes, all featuring the DUF295 domain, were found to harbor an F-box motif at their N-termini, which is implicated in stamen development. Additionally, in transgenic Arabidopsis flowers, genes implicated in tapetum formation and anther development were also observed to be upregulated, implying a potential role for MSL-lncRNAs in modulating pollen development through the positive regulation of these genes. The findings from this study establish a theoretical framework for elucidating the genetic control exerted by MSL-lncRNAs over stamen and pollen development. [ABSTRACT FROM AUTHOR]

Background: 46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive. Methods: We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10). Results: We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7–2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size. Conclusion: This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome. Plain English summary: Our sex chromosome constitution determines our sex, with the presence of a Y chromosome causing male sex determination (typically 46,XY) and the lack hereof resulting in female sex development (typically 46,XX). However, individuals can become male despite of them presenting with the classical female chromosome constitution. We term this "46,XX testicular disorder/difference of sex development" or "46,XX DSD" for short. Individuals with this condition are affected by a number of traits, such as infertility, short stature and altered hormone levels. We know that most cases of 46,XX DSD are caused by the sex-determining region of the Y chromosome being moved to one of the X chromosomes. However, we do not know the more precise size of the Y-chromosomal section or its effects on the genome. In this study we investigated 11 individuals with 46,XX DSD using novel and precise techniques than previously applied. Analyzing DNA, we found that their Y-chromosomal sections varied. This was reflected in multiple types of additional genetic analyses, investigating modifications to DNA and expression of genes. Our findings are the most accurate description of the Y-chromosomal section in 46,XX DSD to date, and indicate that the genomes of individuals with 46,XX DSD differ, with many potential mechanisms of action. Highlights: • From a cohort of 11 individuals with 46,XX testicular DSD, the profile of Y chromosome segments was described in more detail than previously and used to sub-categorize subjects into four groups; SRY-negative, short Yp (2.7–2.8 Mb), medium Yp (7.3 Mb) and long Yp. • In individuals with long Yp segments, a characteristic loss of AMELY, TBL1Y and in some cases PRKY was observed. • Variable expression of the X-Y homologous gene pair PRKX and PRKY was observed, suggesting a compensatory mechanism. • The lengths of Y chromosome segments were reflected in the transcriptome and methylome. • Differential expression and methylation of autosomes suggested genome-wide effects. [ABSTRACT FROM AUTHOR]

The MiniMUGA genotyping array is a popular tool for genetic quality control of laboratory mice and genotyping samples from most experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve the array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA. Here, we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for classical inbred strains and substrains, and increase the number of constructs reliably detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have updated the layout of the report to simplify the interpretation and completeness of the analysis and added a section summarizing the ideogram in table format. These changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research. [ABSTRACT FROM AUTHOR]

Chromosome alignment on the metaphase plate is a conserved phenomenon and is an essential function for correct chromosome segregation for many organisms. Organisms with naturally-occurring trivalent chromosomes provide a useful system for understanding how chromosome alignment is evolutionarily regulated, as they align on the spindle with one kinetochore facing one pole and two facing the opposite pole. We studied chromosome alignment in a praying mantid that has not been previously studied chromosomally, the giant shield mantis Rhombodera megaera. R. megaera has a chromosome number of 2n = 27 in males. Males have X1, X2, and Y chromosomes that combine to form a trivalent in meiosis I. Using live-cell imaging of spermatocytes in meiosis I, we document that sex trivalent Y chromosomes associate with one spindle pole and the two X chromosomes associate with the opposing spindle pole. Sex trivalents congress alongside autosomes, align with them on the metaphase I plate, and then the component chromosomes segregate alongside autosomes in anaphase I. Immunofluorescence imaging and quantification of brightness of kinetochore–microtubule bundles suggest that the X1 and X2 kinetochores are associated with fewer microtubules than the Y kinetochore, likely explaining the alignment of the sex trivalent at the spindle equator with autosomes. These observations in R. megaera support the evolutionary significance of the metaphase alignment of chromosomes and provide part of the explanation for how this alignment is achieved. [ABSTRACT FROM AUTHOR]

Turner syndrome (TS) is a genetic condition in phenotypic females in which the individual has 1 intact X chromosome and the second sex chromosome is absent or structurally altered Components of Y chromosome (eg, 45,X/46,XY) have been found in 5%-15% of patients with TS; these patients are often referred to as having "Turner syndrome with Y" (TS+Y). The presence of Y chromosome material increases risk for development of gonadal tumors. Historically, prophylactic gonadectomy has been recommended in this population to prevent malignancy, and patients were presumed infertile due to the presence of streak gonads with no germ cells (GCs). More recently, studies have reported on spontaneous puberty and menarche in TS+Y patients suggesting the presence of viable GC and ovarian function. Our institution offers patients with TS+Y the option of experimental gonadal tissue cryopreservation (GTC) at the time of gonadectomy. We present a unique case of a young girl with TS+Y who had GCs present in her gonads and underwent experimental GTC at the time of gonadectomy. [ABSTRACT FROM AUTHOR]

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations. [ABSTRACT FROM AUTHOR]

Two methods for preimplantation genetic testing (PGT) have been described for equine embryos: trophoblast cell biopsy (TCB) or blastocoele fluid aspiration (BFA). While TCB is widely applied for both in vivo - and in vitro -produced embryos, BFA has been mostly utilized for in vivo -produced embryos. Alternative methods for PGT, including analysis of cell-free DNA (CFD) in the medium where in vitro -produced embryos are cultured, have been reported in humans but not for equine embryos. In Experiment 1, in vivo - (n = 10) and in vitro -produced (n = 13) equine embryos were subjected to BFA, cultured for 24 h, then subjected to TCB, and cultured for additional 24 h. No detrimental effect on embryonic diameter or re-expansion rates was observed for either embryo group (P > 0.05). In Experiment 2, the concordance (i.e., agreement on detecting the same embryonic sex using two techniques) among BFA, TCB, and the whole embryo (Whole) was studied by detecting the sex-determining region Y (SRY) or testis-specific y-encoded protein 1 (TSPY) (Y-chromosome), and androgen receptor (AR ; X-chromosome) genes using PCR. Overall, a higher concordance for detecting embryonic sex was observed among techniques for in vivo -produced embryos (67–100 %; n = 14 embryos) than for in vitro -produced embryos (31–92 %; n = 13 embryos). The concordance between sample types increased when utilizing TSPY (77–100 %) instead of SRY (31–100 %) as target gene. In Experiment 3, CFD analysis was performed on in vitro-produced embryos to determine embryonic sex via PCR (SRY [Y-chromosome] and amelogenin – AMEL [X- and Y-chromosomes]). Overall, CFD was detected in all medium samples, and the concordance between CFD sample and the whole embryo was 60 % when utilizing SRY and AMEL genes. In conclusion, equine embryos can be subjected to two biopsy procedures (24 h apart) without apparent detrimental effects on embryonic size. For in vivo -, but not for in vitro -produced equine embryos, BFA can be considered a potential alternative to TCB for PGT. Finally, CFD can be further explored as a non-invasive method for PGT in in vitro produced equine embryos. • Equine in vivo- and in vitro -produced embryos were subjected to two biopsies. • An apparent negative effect on embryonic diameter was not observed. • TSPY was more efficient than SRY as a target gene for sex determination of equine embryos. • Blastocele fluid aspiration yielded similar results to trophoblast cells for in vivo embryos. • Cell-free DNA can be isolated from spent medium where in vitro embryos are cultured. [ABSTRACT FROM AUTHOR]

Copyright of Forensic Science & Technology is the property of Institute of Forensic Science, Ministry of Public Security and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Forensic Science & Technology is the property of Institute of Forensic Science, Ministry of Public Security and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Do different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders. Methods: Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)—Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences. Results: We show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r =.75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ. Conclusions: This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior. [ABSTRACT FROM AUTHOR]

Abstract The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome complement). FCG mice have illuminated distinct effects of gonadal and chromosomal sex on traits ranging from brain structure and behavior to vulnerability to obesity, atherosclerosis, multiple sclerosis, Alzheimer’s and other diseases. A recent study determined that the Y Sry− chromosome used in a specific line of C57BL/6J FCG mice harbors nine genes that have been duplicated from the X chromosome. This report raised concern that scores of publications that previously used the FCG model may therefore be flawed, but did not provide details regarding how studies can be evaluated for potential impact (or lack of impact) of the translocation. Here we (1) provide a practical description of the genetic translocation for researchers using the FCG model, (2) document that a majority of the studies cited in the recent report are unlikely to be affected by the translocation, (3) provide a scheme for interpreting data from studies with FCG mice harboring the Y Sry− translocation, and (4) delineate expression levels of the nine translocated genes across tissue/cell types as a filter for evaluating their potential involvement in specific phenotypes.

The Nivkhs are a small ethnic group indigenous of the Russian Far East, living in the Khabarovsk Territory and on Sakhalin Island, descending from the ancient inhabitants of these territories. In the Nivkhs, a specific Sakhalin-Amur anthropological type is prevalent. They are quite isolated, due to long isolation from contacts with other peoples. The gene pool of the Nivkhs and other Far Eastern and Siberian populations was characterized using a genome-wide panel of autosomal single-nucleotide polymorphic markers and Y chromosome haplogroups. Bioinformatic processing of frequencies of autosomal SNPs, Y chromosome haplogroups and YSTR haplotypes showed that the Nivkh gene pool is very different from the other populations’. Analysis of the SNP frequencies using the PCA method divided the Far Eastern populations in full accordance with the territories of their residence into the northern group of the Chukchi and Koryaks and the southern group, including the Nivkhs and Udege. The remoteness of the Nivkhs coincides with their geographic localization, with the Nivkhs and Udege demonstrating the greatest kinship. The Nivkhs have a specific component of their gene pool, which is present with much less frequency in the Udege and Transbaikal Evenks. According to the IBD blocks, the genotypes of the Nivkhs show a very small percentage of coincidence with the Udege, Koryaks, Evenks and Chukchi, the value of which is the lowest compared to the IBD blocks among all other Siberian populations. The Nivkh-specific composition of haplogroups and YSTR haplotypes was shown. In the Nivkhs, the C2a1 haplogroup is divided into three sublines, which have a fairly ancient origin and are associated with the ancestors of modern northern Mongoloids. The Nivkh haplogroup O2a1b1a2a-F238 is found among residents of China and Myanmar. The Q1a1a1-M120 line is represented among the Nivkhs, Koryaks, Evenks and Yukaghirs. Phylogenetic analysis of individual Y chromosomal haplogroups demonstrated the closeness of the Nivkh gene pool with the ancient population of the Amur and Okhotsk regions, the Koryaks, the Tungus peoples and the population of Southeast Asia. The Nivkh gene pool confirms the relative smallness of their ancestral groups without mixing with other populations.

Abstract Background Chromoanagenesis is an umbrella term used to describe catastrophic “all at once” cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline. The clinical features associated with constitutional chromoanagenesis are typically due to copy number changes and/or disruption of genes or regulatory regions. Case presentation We present an 8-year-old male patient with complex rearrangements of the Y chromosome including a ring Y chromosome, a derivative Y;21 chromosome, and a complex rearranged Y chromosome. These chromosomes were characterized by G-banded chromosome analysis, SNP microarray, interphase FISH, and metaphase FISH. The mechanism(s) by which these rearrangements occurred is unclear; however, it is evocative of chromoanagenesis. Conclusion This case is a novel example of suspected germline chromoanagenesis leading to large copy number changes that are well-tolerated, possibly because only the sex chromosomes are affected.

In the organisms with XX/XY sex chromosomes, Y chromosome is unique to males and plays an important role in male reproductive development. The study of Y chromosome genes will contribute to the development of pest genetic prevention and control technology. In this study, we identified 9 Y chromosome genes in Zeugodacus tau (Diptera: Tephritidae), including gene 16222. Protein structure analysis showed that 16222 was highly similar to odorant binding protein, and thus gene 16222 was named obp‐Y. Obp‐Y knockout (KO) significantly reduced hatching rate of offspring. Sperm detection results showed that obp‐Y KO did not affect sperm number in the testes or sperm transfer during mating. We further examined the storage of sperms in females, and found that sperms in females mating with wild‐type males began to transfer from spermathecal ducts to the spermathecae at hour 0 after the end of mating (AEM), and at 0–24 h AEM, the sperm count in the spermathecae gradually increased. However, no sperms were observed in spermathecae of females mating with mutant males at hours 0, 4, 8, 24 and 48 AEM. In summary, this study revealed that Y chromosome gene obp‐Y was necessary for the storage of sperms in females. Our findings not only provide theoretical basis for elucidating the function of the Y chromosome, but also offer a molecular target for the genetic control over Z. tau. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion In this study, we aim to explore the genetic imprint of Bronze Age globalization in East Asia from a phylogeographic perspective by examining the Y‐chromosome haplogroup Q1a1a‐M120, and to identify key demographic processes involved in the formation of early China and the ancient Huaxia people.Over the past few decades, we have collected the sequences of 347 Y chromosomes from the haplogroup Q1a1a‐M120. These sequences were utilized to analyze and reconstruct a highly revised phylogenetic tree with age estimates. And we analyzed the geographical distribution and spatial autocorrelation of nine major sub‐branches of Q1a1a‐M120. Finally, we observed the expansion of Q1a1a‐M120 from the beginning of the Bronze Age in East Asia, along with the continuous dissemination of its sub‐lineages among East Asian populations.We suggest that certain sub‐lineages played a significant role in the formation of states and early civilizations in China, as well as in the development of the ancient Huaxia people, who are the direct ancestors of the Han population. Overall, we propose that haplogroup Q‐M120 played a role in the introduction of Bronze Age culture to the central region of East Asia. Therefore, it is haplogroup Q‐M120, rather than the Western Eurasian paternal lineage, that expanded and contributed to the gene pool of the East Asian population.In summary, the globalization of the Bronze Age led to large‐scale population replacement and admixture across various regions of Eurasia; our findings highlight the unique demographic processes that occurred in East Asia during this period. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Blood Cancer Journal that discusses the global burden of Burkitt lymphoma (BL) from 1990 to 2021 and makes predictions for 2030. BL is a highly aggressive form of non-Hodgkin lymphoma that primarily affects young males. The incidence rates of BL vary significantly across different continents, with the highest rates found in equatorial Africa. Survival outcomes for BL are influenced by factors such as disease stage, geographic location, ethnicity, and treatment approaches. The document presents data on incident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs) of BL, as well as age-standardized rates, and analyzes trends and shifts in these metrics. The findings show an upward trend in all metrics for BL from 1990 to 2021, with significant shifts in incidence and prevalence occurring in certain years. The document also examines the relationship between socioeconomic factors and BL rates and provides projections for BL numbers and rates until 2030. The given text provides a series of numerical values for various regions around the world, including their mortality rates, years of life lost, and disability-adjusted life years. The regions covered include Central Europe, Central Latin America, Central Sub-Saharan Africa, East Asia, Eastern Europe, Eastern Sub-Saharan Africa, High-income Asia Pacific, High-income North America, North Africa and Middle East, Oceania, South Asia, Southeast Asia, and Southern Latin America. These values can be used [Extracted from the article]

BACKGROUND: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease. METHODS: LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed. RESULTS: In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.234.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events. CONCLUSIONS: LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events. [ABSTRACT FROM AUTHOR]

A total of 154 Emirati infertile patients were included in this study of which a cohort of 18 infertile males undergoing fertility counseling were recruited from Dubai Fertility Center (DFC) and University Hospital of Sharjah (UHS), in addition to136 azoospermic Emirati infertile patients who performed AZF-deletion screening as counselled and recorded by DFC during the period of January 2011 and January 2021. Diagnostic screening was conducted to investigate the frequency of microdeletion in the Azoospermia Factor (AZFa, AZFb, AZFc, AZFd) gene cluster of the Y-chromosome among Emirati infertile male patients using the Sequences-Tagged-Sites (STS)-Multiplex PCR diagnostic technology. The frequency of the AZF microdeletions was 2.2% as detected in three patients with azoospermia (n=3/136). There were two complete deletions in the AZFc region as shown by deletion of the two STS; SY254 (380 bp) and SY255 (124 bp). Our findings are similar to those reported in regional and global range, which appeared to vary across genealogical-lineages in different geographical landscape. This article is the first to profile AZF microdeletions in Emirati Azospermic males, offering valuable insights into male infertility genomics worldwide. The novelty and importance of the findings are especially relevant for improved healthcare and male infertility in Gulf countries due to shared tribal genetic lineage. This highlights the importance of the screening for the AZF-deletion for male infertility diagnosis for better management and treatments in the fertility clinics and hospitals in the UAE. [ABSTRACT FROM AUTHOR]